Influence of Dietary Fish Oil on Granulomatous Inflammation in the Lung Following Inhalation of Silica and Infection with Bacillus Calmelte-Guerin

Abstract

Recent evidence has suggested that fish oil diets, in addition to purported beneficial effects on the cardiovascular system, may also act to modulate inflammatory and immunologic reactions. These actions may be due to an increased content in fish oils of the n-3 fatty acid, eicosapentaenoic acid, which can competitively inhibit the production of arachidonic acid metabolites, forming 3-series prostaglandins and 5-series leukotrienes. In many cases these metabolites are not as biologically active as those formed from arachidonic acid. We examined the effects of dietary fish oil on granu-lomatous lesion development, pulmonary adherent cell (macrophage) activity, and arachidonic acid metabolite production following a regimen of silica inhalation and infection with Bacillus Calmette-Guerin (BCG). Mice on diets containing 10% corn oil or a mixture of 9% fish and 1% corn oils were placed in silica inhalation chambers for 6 wk, infected with BCG, and returned to inhalation chambers. Control animals, on either fish or corn oil diets, breathed filtered air. At varying times thereafter (1 day, 6 wk, 29 wk) animals were sacrificed and adherent cells, primarily macrophages, were obtained by lung teasing and adherence. The state of activation of these cells was assessed, as well as their ability to produce arachidonic acid metabolites following stimulation with zymosan. At the last time point a detailed histological examination of the lung was made that included morphometric measurement of the lesions. Morpho-metric analysis of lesion development showed significantly increased lesion severity in the lungs of the silica or BCC mice being fed the fish oil diets. It was found that macrophages from mice on the fish oil diet produced significantly less leukotriene B, (LTB₄) and thromboxane B₂ than did those on the corn oil diet. The ability of cells to produce LTB, after exposure to silica and BCG depended on length of time after exposure. LTB, production was decreased at the 1 day time point, whereas at both 6 and 29 wk after BCG exposure it was increased. Macrophage activation in the silica/BCG-treated animals was indicated by a significant decrease in S′-nucleotidase activity.